Reconstructing DNA methylation maps of ancient populations

Arielle Barouch, Yoav Mathov, Eran Meshorer, Benjamin Yakir, Liran Carmel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Studying premortem DNA methylation from ancient DNA (aDNA) provides a proxy for ancient gene activity patterns, and hence valuable information on evolutionary changes in gene regulation. Due to statistical limitations, current methods to reconstruct aDNA methylation maps are constrained to high-coverage shotgun samples, which comprise a small minority of available ancient samples. Most samples are sequenced using in-situ hybridization capture sequencing which targets a predefined set of genomic positions. Here, we develop methods to reconstruct aDNA methylation maps of samples that were not sequenced using high-coverage shotgun sequencing, by way of pooling together individuals to obtain a DNA methylation map that is characteristic of a population. We show that the resulting DNA methylation maps capture meaningful biological information and allow for the detection of differential methylation across populations. We offer guidelines on how to carry out comparative studies involving ancient populations, and how to control the rate of falsely discovered differentially methylated regions. The ability to reconstruct DNA methylation maps of past populations allows for the development of a whole new frontier in paleoepigenetic research, tracing DNA methylation changes throughout human history, using data from thousands of ancient samples.

Original languageAmerican English
Pages (from-to)1602-1612
Number of pages11
JournalNucleic Acids Research
Issue number4
StatePublished - 28 Feb 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.


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